case report varicella zoster virus meningitis in a young

Case ReportVaricella Zoster Virus Meningitis in a Young ImmunocompetentAdult without Rash: A Misleading Clinical Presentation

Thomas Pasedag,1,2 Karin Weissenborn,1 Ulrich Wurster,1 Tina Ganzenmueller,3

Martin Stangel,1 and Thomas Skripuletz1

1Department of Neurology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany2Department of Psychiatry and Psychotherapy, Klinikum Region Hannover, Rohdehof 3, Langenhagen, Germany3Institute of Virology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany

Correspondence should be addressed toThomas Skripuletz; [email protected]

Received 1 October 2014; Revised 10 December 2014; Accepted 14 December 2014; Published 29 December 2014

Academic Editor: Dominic B. Fee

Copyright © 2014 Thomas Pasedag et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Meningitis caused by varicella zoster virus (VZV) is rare in healthy population. Predominantly immunocompromised patients areaffected by reactivation of this virus with primary clinical features of rash and neurological symptoms. Here we report a youngotherwise healthy man diagnosed with a VZV meningitis without rash. He complained of acute headache, nausea, and vomiting.The clinical examination did not show any neurological deficits or rash. Cerebrospinal fluid (CSF) analysis revealed a high leukocytecell count of 1720 cells/𝜇L and an elevated total protein of 1460mg/L misleadingly indicating a bacterial infection. Further CSFanalyses, including polymerase chain reaction (PCR) and detection of intrathecal synthesis of antibodies, showed a VZV infection.Clinical and CSF follow-up examinations proved the successful antiviral treatment. In conclusion, even young immunocompetentpatients without rash might present with VZV meningitis. CSF examination is a key procedure in the diagnosis of CNS infectionsbut in rare cases the standard values cell count and total protein might misleadingly indicate a bacterial infection.Thus, virologicalanalyses should be considered even when a bacterial infection is suspected.

1. Introduction

Infections with neurotropic herpes viruses (herpes simplextype 1/2, varicella zoster virus (VZV)) are frequent in humans.These viruses persist within cranial nerves, dorsal roots, andautonomic ganglia causing latent infections with the abilityof reactivation [1–3]. Reactivation of VZV shows mainlya herpes zoster presenting with rash and pain affectingthe entire dermatome and less frequently a zoster sineherpete [1–3]. VZV infection of the central nervous system(CNS) such as encephalitis, meningitis, myelitis, or angiitisoccurs less frequently but is feared because of the numerousunfavourable outcomes [1, 3, 4]. Usually CNS infection withVZV comes along with dermal affection but can rarelydevelop without rash [1, 3, 5–10].

Acute infection orVZV reactivation affects predominant-ly older individuals and/or immunocompromised patients[1–3, 9]. CNS infection with VZV in young healthy adults

is rare and is unexpected and only very few cases have beendescribed so far [5–9]. Here, we describe a young previouslyhealthy man with VZV meningitis who had only minimalsymptoms.

2. Case Presentation

An 18-year-old man experienced severe occipital headacheaccompanied by nausea and vomiting. All symptoms startedimmediately after a backward roll doing judo exercise. Treat-ment with paracetamol, acetylsalicylic acid, and metamizoledid not show beneficial effects. Thus, he presented to ouremergency room nine days after the first symptoms.

The physical examination was normal. Particularly, stiffneck as a typical sign of meningitis was not found and he didnot show any rash. He had never been sick before and didnot take any medications regularly. Furthermore, he did notsmoke or drink alcohol excessively.

Hindawi Publishing CorporationCase Reports in Neurological MedicineVolume 2014, Article ID 686218, 4 pageshttp://dx.doi.org/10.1155/2014/686218

2 Case Reports in Neurological Medicine

Table1:ClinicalandCS

Ffin

ding

sinim

mun

ocom

petent

patie

ntsw

ithVZV

meningitis

with

outrash.Qalb:albu

min

quotient

(CSF

albu

min/serum

albu

min),OCB

:oligoclonalb

ands,and

ASI:antibod

yspecificind

ex((CS

FVZV

-IgG/serum

VZV

-IgG)/(C

SFtotal-IgG

/serum

total-IgG

)).M

RIresults

ofpatie

nt4:MRI

revealed

anill-definedT2

hyperin

tensity

inther

ight

frontal

lobe,extending

from

thec

orticalsurfa

ceto

thefrontalho

rnof

thelateralventric

lewith

outm

asse

ffect,con

sistent

with

aham

artomao

rcorticaldysplasia

.Afollo

w-upMRI

with

gado

linium

onday10

was

norm

al,w

ithno

change

inthes

olitary

T2hyperin

tensity.

Patie

ntsAge/

gend

erSymptom

sDurationof

symptom

s(days)

Clinicalsig

nsPrevious

diseases

Brainim

aging

Cerebrospinalflu

idRe

ference

Cells/𝜇L

Cells

(%)

Protein

(mg/L)

Lactate

(mmol/L)

Qalb

OCB

VZV

DNA

VZV

ASI

118/m

ale

Headache,

nausea,

vomiting

9Ex

amination

norm

al,no

rash

Non

eMRI:n

ormal

1720

96%

lymph

ocytes,3%

plasmac

ells,

1%mon

ocytes

1460

3.0

19.7

Type

350

000

copies/m

L74.9

Our

case

Nosymptom

s48

Exam

ination

norm

al,no

rash

Non

en.d.

1995%

lymph

ocytes,5%

mon

ocytes

613

1.68.1

Type

3Negative

21.5

Our

case

253/fe

male

Headache,

nausea,

photop

hobia,

generalized

body

aches

3Ex

amination

norm

al,no

rash

Diabetes

mellitus,

bron

chial

asthma,

bipo

lar

disease

CT:m

ildatroph

y923

98%

lymph

ocytes,2%

mon

ocytes

1650

3.1

n.d.

n.d.

Positive

n.d.

Klein

etal.,2010

[8]

312/m

ale

Headache

4Ex

amination

norm

al,no

rash

Bron

chial

asthma

CT:n

ormal

590

97%

lymph

ocytes,1%

mon

ocytes,2%

neutroph

ils

860

n.d.

n.d.

n.d.

Positive

n.d.

Jhaverietal.,2003

[5]

426/fe

male

Headache,

nausea,

photop

hobia,

vomiting

6Ex

amination

norm

al,no

rash

Non

eMRI

(see

legend

)331

99%

mon

onuclear

2190

n.d.

n.d.

n.d.

1270

00copies/m

Ln.d.

Habibetal.200

9[7]

514/m

ale

Headache,

photop

hobia,

vomiting

7Ex

amination

norm

al,no

rash

Migraine

MRI:n

ormal

285

n.d.

1580

n.d.

n.d.

n.d.

Positive

n.d.

Leahyetal.,2008

[6]

Case Reports in Neurological Medicine 3

Subarachnoid hemorrhage or dissection of cerebral arter-ies was first considered. Magnetic resonance imaging (MRI)scan of the brain showed no abnormalities such as bleeding,infarction, or malignancy. Additional MR-angiography andultrasound examination of carotid, vertebral, and intracra-nial arteries revealed no vascular alterations. Measure-ments of body temperature and blood pressure as wellas laboratory urine and blood examinations (blood count,sodium, potassium, C-reactive protein, creatinine, transam-inases, creatinine kinase, serum protein electrophoresis,thyroid-stimulating hormone, thyroxine, triiodothyronine,anti-thyroid autoantibodies (anti-thyroid peroxidase anti-bodies, thyrotropin receptor antibodies, and thyroglobulinantibodies), anti-nuclear antibodies, anti-neutrophil cyto-plasmic antibodies, anti-cardiolipin antibodies, angiotensin-converting enzyme, and amount of vitamins B12, B6, and B1)showed normal results.

CSF analysis revealed a high leukocyte cell count of 1720cells/𝜇L and an elevated total CSF protein of 1460mg/L.Furthermore, slightly elevated CSF lactate concentration of3.0mmol/L and a slightly reduced CSF glucose concentrationof 42mg/dL were found. Considering a bacterial infection,intravenous treatment with ceftriaxone (2 g/day) and ampi-cillin (15 g/day) was applied.

Cytologic analysis of the CSF revealed 3% plasma cells.The remaining cells were predominantly lymphocytes withnormalmorphology. FurtherCSF abnormalities included ele-vated albumin quotient (QAlb) indicating a moderate blood-CSF-barrier-dysfunction (Table 1). Intrathecal immunoglob-ulin (Ig) synthesis of IgG, IgM, and IgA as calculated basedon the method of Reiber-Felgenhauer [11] was not found.Oligoclonal bands restricted to the CSF were identifiedindicating intrathecal IgG synthesis in the CSF. Furthermore,identical oligoclonal IgG bands in CSF and serumwere foundindicating a systemic humoral immune response towardsforeign antigens and/or self-antigens.

Microbiological analyses did not detect any bacterialinfection. Further analyses for Borrelia burgdorferi, Tre-ponema pallidum, Mycobacterium tuberculosis, toxoplasmo-sis, Candida, and Cryptococcus neoformans showed negativeresults. Virological examinations presented negative resultsfor herpes simplex virus, cytomegalovirus, Epstein-Barrvirus, enteroviruses, tick-borne encephalitis, human immun-odeficiency virus, and hepatitides B, C, and A. Quantitativereal-time PCR analysis [12] of the CSF revealed presence ofVZV-DNAwith a concentration of 50.000 copies/mL indicat-ing high viral replication. Thus, one day after antibiotic ther-apy the patient was treatedwith acyclovir (2250mg/day intra-venously for 11 days), followed by valacyclovir (3000mg/dayorally for 5 days). Additionally, we measured the intrathecalsynthesis [13] of VZV immunoglobulin G antibodies (Enzyg-nost Anti-VZV/IgG, Siemens Healthcare Diagnostics) andfound a specific antibody index (AI) of 74.9 (normal value< 1.5). The presence of a strong intrathecal IgG productionagainst VZV confirmed the VZV infection in the CNS.

Eleven days after intravenous therapy, the patient wasdischarged feeling well. Follow-up CSF examination wasperformed 23 days after the end of antiviral treatment. Aslight pleocytosis with 19 cells/𝜇L was still found. Plasma

cells were not found and lymphocytes andmonocytes showednormal morphology. VZV-PCR was negative but a persistingintrathecal IgG production to VZV (specific antibody indexof 21.5) indicated a preceding VZV infection. The patient feltwell without any symptoms. He practiced judo again fourtimes per week.

3. Discussion

Here we present a young previously healthy man with aVZV meningitis without rash. This case is extraordinarybecause the clinical presentation was unusual for a patientwith meningitis and the initial CSF findings with very highpleocytosis and elevated total CSF protein initially mislead-ingly suggested a bacterial infection. Interestingly, furtherCSF examinations detected a VZV infection.

Our case underlines the importance of specialised CSFdiagnostics in acute neurological emergency situations. CSFexamination is generally considered a key procedure in thediagnosis of CNS infections [14]. Using sensitive laboratoryanalyses (e.g., PCR and detection of intrathecal produc-tion of specific antibodies) recent epidemiological studiesfound a portion of 5–29% of VZV in aseptic meningitisand encephalitis and it was suspected that VZV infectionshad been underestimated in earlier publications [9, 15–18].Nevertheless in immunocompetent patients without rash andneurological deficits (as in our case) VZV meningitis seemsto be rare and only few cases have been described to date(see Table 1). Infections of the CNS are accompanied byan elevated cell count in the CSF. In large series includingpatients with aseptic meningitis and encephalitis CSF find-ings predominantly revealed lymphomonocytic pleocytosisof less than 500 cells/𝜇L, mild to moderately elevated totalprotein, and normal lactate levels [16–18]. In patients withVZV infection median cell counts of 43/𝜇L, 132/𝜇L, 286/𝜇L,and 293/𝜇L were found and the cell counts ranged from15 to 840 cells/𝜇L [9, 16–18]. In our case, we found thehighest pleocytosis (1720 cells/𝜇L) that has been described forthis group of patients. In addition, total protein and lactateconcentrationwere elevated leading to amisleading diagnosisof bacterial meningitis.

In conclusion, even young and previously healthy patientswithout clinical features of dermal irritation such as rashmight present with VZV meningitis. We highlight theimportance of considering VZV as a possible cause formeningitis even in previously healthy young patients andthe recommended diagnostic lumbar puncture. DetailedCSF diagnostic procedures including PCR and detection ofintrathecal synthesis of antiviral antibodies (especially forVZV and HSV) should be considered even though CSF cellcount and total protein seem to indicate a bacterial infection.

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper.

4 Case Reports in Neurological Medicine

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